Liver - Inflammation

Inflammation, focal is the term used to denote single or multiple, focal, randomly distributed aggregates of inflammatory cells that are seen in the liver as a background lesion and are more frequent in aging mice and rats than in young animals. However, these foci of inflammatory cells can occur spontaneously in livers of rodents in prechronic studies (Figure 1 and Figure 2). The infiltrating cells are predominantly lymphocytes but may include fewer numbers of neutrophils and/or macrophages. Inflammatory cell aggregates may be accompanied by evidence of hepatocellular necrosis (Figure 3 and Figure 4). These foci may vary in size (Figure 6 and Figure 7) but typically are not grossly apparent. These lesions may be more common in females (Harada et al. 1996) and may be related to infectious agents (Hall et al. 1992). Most often the cause is unknown. If only one or two foci of inflammation are seen in the standard histologic sections, the severity grade would be 1+ (minimal). Xenobiotic exposure may also increase the severity and/or number of these lesions compared with concurrent controls.

Focal inflammation is the most frequently seen inflammatory lesion of the liver in rodent toxicity studies and is a form of chronic inflammation. In chronic inflammation, lymphocytes predominate. Chronic active inflammation predominately involves lymphocytes as well but also includes a significant number of neutrophils. Both lesions may contain macrophages. However, the term “chronic inflammation” or “chronic active inflammation” may be used only if the lesion differs in some qualitative way from the above description of “inflammation, focal.”

Other less common forms of inflammation include acute, suppurative, and granulomatous inflammation. In acute inflammation, neutrophils are the predominant infiltrating cell, though fewer macrophages and lymphocytes may also be present, as well as evidence of edema or hyperemia. In suppurative inflammation, neutrophils are also the predominant infiltrating cell type but they are aggregated, and many are degenerate. Cell debris from both the resident cell populations and infiltrating leukocytes may also be present in the exudate, as well as proteinaceous fluid containing fibrin, a few macrophages, occasional lymphocytes or plasma cells, and possibly an infectious agent. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Granulomatous inflammation is another form of chronic inflammation whose diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, and/or multinucleated giant cells.

The term “cellular infiltrate” has been used to describe the presence of inflammatory cells without other evidence of an inflammatory process (e.g., edema, necrosis or degeneration of cells, or evidence of vascular injury). Such infiltrates of inflammatory cells are generally quite small and may not warrant diagnosis. If significant enough to warrant documentation, accumulations of leukocytes should be diagnosed as “inflammation.” Occasionally, infiltrates of nonleukocytic cells such as mast cells are seen in the liver; these should be diagnosed as “cellular infiltrate.”